Biochemical, structural, and cellular studies reveal Jumonji-C (JmjC) domain-containing (JMJD7) as a 2-oxoglutarate (2OG)-dependent oxygenase catalyzing a previously unreported type of post translational modification, (3S)-lysyl hydroxylation. Crystallographic analyses reveal JMJD7 as more closely related to the JmjC hydroxylases rather than the JmjC demethylases. Biophysical and mutation studies show that JMJD7 has a unique dimerization mode, with interactions between monomers involving both N- and C-terminal regions and disulfide bond formation. A proteomic approach identifies two related members of the Translation Factor (TRAFAC) family of GTPases, Developmentally Regulated GTP Binding Proteins 1 and 2 (DRG1/2), as activity-dependent JMJD7 interactors. Mass spectrometric analyses demonstrate that JMJD7 catalyzes Fe(II)- and 2OG-dependent hydroxylation of a highly-conserved lysine residue in DRG1/2; amino acid analyses reveal JMJD7 catalyzes (3S)-lysyl hydroxylation. The functional assignment of JMJD7 will enable future studies to define the role of DRG hydroxylation in cell growth and disease.
MSQ506 - hydroxylation of DRG1/2 detected after assay with Jmjd7 wt, H178A mutant and empty vector (analysed with Q-Exactive classic, Progenesis QI and Mascot)
MSQ784 - as above (analysed Q-Exactive classic, Progenesis QI and PEAKS)
MSQ849 - Hydroxylation of endogenous DRG (analysed with Q-Exactive HF and PEAKS)
MSQ884 - as above (analysed with Orbitrap Fusion Lumos and PEAKS)
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: JMJD7, Hydroxylation
Principal Investigators: (in alphabetical order) |
Mathew Coleman, University of Birmingham, United Kingdom |
Submitting User: | romanfischer |
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